Self-adhesive film for teeth

ABSTRACT

Mono- or multilayered, film-shaped, pressure-sensitive adhesive preparations for application in the oral region and a process for manufacturing such preparations. The preparations contain at least one poly-methylvinylether-maleic acid anhydride copolymer, polyvinyl acetate and/or at least one copolymer of the polyvinyl acetate with vinyl alcohol esters of fatty acids, as well as at least one cosmetic and/or pharmaceutical active substance.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. patent application Ser. No. 11/664,949, filed Apr. 9, 2007, which is a National Stage application of International Patent Application No. PCT/EP2005/010749, filed Oct. 6, 2005, which claims priority to German Patent Application No. DE 10 2004 049 740.0 filed Oct. 13, 2004. Each of U.S. patent application Ser. No. 11/664,949; International Patent Application No. PCT/EP2005/010749; and German Patent Application No. DE 10 2004 049 740.0 are hereby incorporated by reference herein in their entirety.

FIELD OF THE INVENTION

The present invention relates to film-shaped preparations which are pressure-sensitive adhesive to teeth, gums or the oral mucosa and which are suitable for cosmetic or medical treatment of the teeth, especially the tooth necks, and of the gums. In addition, the present invention relates to a process for the manufacture of such film-shaped preparations.

BACKGROUND OF THE INVENTION

Products for cleaning one's mouth and for active substance delivery having the form of pastes, creams or mouth rinses have long since been known and have been available on the market. These products include tooth pastes and creams which have a cleaning effect, protect against caries, are desensitizing, or have a bleaching effect. Also known are creams, gels and ointments that are applied in the oral region for treating local illnesses and disorders such as anti-inflammatory remedies, analgesic remedies and/or tonics.

For some years, film-shaped, flat-shaped or strip-shaped oral application forms, too, have been commercially available and are used for cosmetic or therapeutic purposes. These application forms include, for example, the Listerine Pocket-Paks® by Pfizer or the “Teeth Whitestrips” by Procter & Gamble. Such application forms are as a rule based on films made up of water-soluble polymers which on use disintegrate rather quickly and are therefore not suitable for a longer-lasting treatment.

In addition, products are known that consist of several layers, such as those disclosed in U.S. Pat. No. 6,582,708, which, however, include only one flexible layer and which, due to their overall thickness of up to 3 mm, are disturbing and unpleasant in the mouth.

The recipes and methods used in the manufacture of the known film-shaped application forms, for the most part, start from water or from water-containing alcoholic polymer solutions. A disadvantage here is that there are limitations to preparing a completely dissolved formulation of lipophile, poorly water-soluble active substances or of active substances that are sensitive to water.

SUMMARY OF THE INVENTION

The object of the present invention was thus to provide a mono- or multilayered, water-soluble or at least partially water-swellable film-shaped material which has good adhesion to teeth, gums or the oral mucosa, which is suitable as active substance carrier, and which does not already disintegrate with in a few seconds. More particularly, the object is to provide a film-shaped material of the afore-mentioned type which enables administration of water-insoluble or water-sensitive active substances.

This object is achieved by providing a mono or multilayered, pressure-sensitive-adhesive, film-shaped preparation which contains at least one polymethyl vinyl ether-maleic acid anhydride copolymer, polyvinyl acetate and/or at least one copolymer of the polyvinyl acetate with vinyl alcohol esters of fatty acids, as well as at least one cosmetic and/or pharmaceutical active substance.

DETAILED DESCRIPTION OF THE INVENTION

Preferably, the content of polymethyl vinyl ether-maleic acid anhydride copolymer in the film-shaped, pressure sensitive adhesive preparations is 5 to 35%-wt.

The content of polyvinyl acetate and/or of the copolymer(s) of the polyvinyl acetate with vinyl alcohol esters of fatty acids in the film-shaped, pressure-sensitive-adhesive preparations preferably amounts to 4 to 35%-wt. The film-shaped, pressure-sensitive adhesive preparations in addition have a content of at least one cosmetic and/or pharmaceutical active substance which is determined by the nature of the illness or by the cosmetic needs. The active substance is preferably a poorly water-soluble active substance or a water-sensitive active substance.

It should be appreciated that the term “poorly water-soluble active substances” is understood to mean such active substances as have a solubility in water of less than 1 g/l. These include, for example, griseofulvin, estradiol and vitamin D₃.

The water-sensitive active substances include those active substances, the aqueous solution of which looses more than 0.1% of its active substance content within 24 hours at room temperature due to decomposition of the active substance. The water-sensitive active substances include, for example, acetylsalicylic acid andiodine.

In a particularly preferred embodiment, the film-shaped, pressure-sensitive adhesive preparation in addition contains carboxymethyl cellulose and/or one of its salts. The content of carboxymethyl cellulose or of one of its salts in the preparation amounts to 5 to 35%-wt.

To manufacture the film-shaped preparations, which are pressure-sensitive adhesive on teeth, gums or the oral mucosa, the various, water-soluble and/or water-swellable polymers are mixed with at least one active substance in solutions containing organic solvents as main component. This mixture is used to coat a substrate, and the coated substrate is dried, optionally by application of heat.

The advantages of the invention arise especially where mixtures of polymethyl vinyl ether-maleic acid anhydride co-polymers with polyvinyl acetate, or with copolymers of the latter with vinyl alcohol esters of fatty acids are used.

The content of polymethyl vinyl ether-maleic acid anhydride copolymer is preferably 5 to 35%-wt., and the content of polyvinyl acetate and/or the copolymer(s) of the polyvinyl acetate with vinyl alcohol esters of fatty acids is preferably 4 to 35%-wt., in each case relative to the solids content.

The polymethyl vinyl ether-maleic acid anhydride copolymers sold under the name of Gantrez by the firm of ISP, and the polyvinyl acetates designated as ⁰VINNAPAS or their copolymers with vinyl alcohol esters of fatty acids of the firm of Wacker Polymer Systems, Burghausen, have proved to be particularly suitable in accordance with the present invention.

Any solvents which dissolve the polymethyl vinyl ether-maleic acid anhydride copolymers and polyvinyl acetate or its copolymers with vinyl alcohol esters of fatty-acids may be used as the organic solvents which, in the method according to the invention, are contained in the solution as the main component thereof. Of these organic solvents, those are used with preference which also mix with water since by adding small amounts of water; e.g. of 1 to 5%-wt., the dissolving power for the polymers and the active substance/active substances can be adapted to the given requirements. Particular preference is given to those organic solvents which permit addition of the active substance dissolved in ethanol or in an ethanol-water mixture. The especially preferred organic solvent is selected from the group comprising methyl ethyl ketone, ethyl acetate, ethanol, acetone and mixtures thereof.

The consistency and/or tackiness of the resultant film-shaped preparations can be adapted to the demands placed on the product by altering the mixing ratio of ethanol and methyl ethyl ketone. Solvent mixtures containing an ethanol portion of 5 to 20%-wt., relative to the total solvent, have proved advantageous.

To manufacture a preferred embodiment enabling a particularly successful adhesion of the film-shaped preparations on the teeth, gums and/or oral mucosa, carboxymethyl cellulose and/or at least one of its salts is added to the polymer mixture.

Preferably, 5 to 35%-wt. of carboxymethyl cellulose or at least one of its salts, relative to the solids content, is added to the polymer mixture.

To manufacture the preparation according to the invention, at least one polymethyl vinyl ether-maleic acid anhydride copolymer and polyvinyl acetate and/or at least one copolymer of the vinyl acetate with vinyl alcohol esters of fatty acids, together with at least one active substance and, optionally, carboxymethyl cellulose and/or at least one of its salts, are mixed in a solution containing one or several organic solvents as its main component. The resultant compound is applied in liquid form to a support and freed from the solvent mixture, so that a film having a layer thickness of 4 to 2000 pm, preferably 40 to 500 pm, and particularly preferably 60 to 250 pm, is obtained.

Multilayer, pressure-sensitive-adhesive film-shaped preparations, with which it is possible to achieve, for example, an improved adhesion of the preparation to teeth, can be prepared, for example, by hot lamination, by coating already existent layers with further solvent-containing compounds, as described hereinabove in connection with the manufacture of a monolayer film, or by other processes known to those skilled in the art.

Pieces having a size appropriate to the respective given purposes are then punched out from the film or laminate.

The process according to the present invention results in film-shaped preparations which adhere to teeth, gums or the oral mucosa, which do not already disintegrate within a few seconds, and by means of which water-insoluble and even water-sensitive active substances can be administered. These preparations may advantageously be utilized for medical or cosmetic treatments.

5 g of a 33.3% solution (%-wt.) of a vinyl acetate-based polymer in methyl ethyl ketone and 3 g of a 15% solution (%-wt.) of polymethyl vinyl ether-maleic acid anhydride (=copolymer of methyl vinyl ether and maleic acid anhydride) in ethyl acetate were added together and homogenized. This resulted in a solution which was spread at various coating thicknesses and, subsequently, dried. This yielded flexible films which adhered both to the oral mucosa and to the teeth. 

1. A process for manufacturing a preparation, the preparation being a monolayer or multilayer, film-shaped, pressure sensitive-adhesive preparation for application to the oral region, especially on the teeth, the preparation comprising at least: polyvinyl acetate; a copolymer of the vinyl acetate with vinyl alcohol esters of fatty acids; and/or a polymethyl vinyl ether-maleic acid anhydride copolymer and an additional content of carboxymethyl cellulose and/or at least one salt of said carboxymethyl cellulose; and at least one cosmetic and/or pharmaceutical active substance; said preparation having a solids content, said process comprising the steps of: providing a solvent comprising at least one organic solvent as the main component; mixing at least one of: polyvinyl acetate, a copolymer of the vinyl acetate with vinyl alcohol esters of fatty acids, a polymethyl vinyl ether-maleic acid anhydride copolymer and carboxymethyl cellulose and/or at least one salt of said carboxymethyl cellulose; and at least one cosmetic and/or pharmaceutical active substance in said solvent that contains at least one organic solvent as the main component to form a mixture; coating a substrate with the mixture to form a coating; and drying the coating to remove the solvent.
 2. The process according to claim 1, wherein said copolymer of the vinyl acetate with vinyl alcohol esters of fatty acids is a copolymer of the vinyl acetate with vinyl alcohol esters of lauric acid.
 3. The process according to claim 1, wherein the content of a polymethyl vinyl ether-maleic acid anhydride copolymer is 5 to 35%-wt., relative to the solids content.
 4. The process according to claim 1, wherein the content of polyvinyl acetate and/or of the copolymer(s) of the vinyl acetate with vinyl alcohol esters of fatty acids is 4 to 35 %-wt., relative to the solids content.
 5. The process according to claim 1, wherein said solvent contains 1 to 5%-wt. of water.
 6. The process according to claim 1, wherein the active substance is poorly soluble in water or is sensitive to water.
 7. The process according to claim 8, wherein said at least one organic solvent is selected from the group consisting of methyl ethyl ketone, ethyl acetate, ethanol, acetone and mixtures of ethyl ketone, ethyl acetate, ethanol and acetone.
 8. The process according to claim 7, wherein said at least one organic solvent is a mixture of ethanol and methyl ethyl ketone.
 9. The process according to claim 8, wherein the mixture has an ethanol content of 5 to 20%-wt.
 10. The process according to claim 1, further comprising the step of adding said carboxymethyl cellulose and/or said at least one salt of carboxymethyl cellulose to the mixture before, the step of coating said mixture onto said substrate.
 11. The process according to claim 10, wherein the content of carboxymethyl cellulose and/or said at least one salt of carboxymethyl cellulose is 5 to 35%-wt. relative to the solids content.
 12. The process according to claim 1, further comprising the step of applying at least one additional layer after the step of drying the coating, wherein said at least one additional layer is applied to the existing layer(s) by hot lamination or by coating the existing layer(s) with at least one solvent-containing compound.
 13. The process according to claim 1, and further comprising the steps of applying, the compound onto said substrate, and drying the compound to obtain the mixture with a layer thickness of 4 to 2000 μm.
 14. The process according to claim 13, wherein, the layer thickness after the drying step is 40 to 500 μm.
 15. The process according to claim 14, wherein, the layer thickness after the drying step is 60 to 250 μm.
 16. Use of a preparation manufactured according to claim 1 for cosmetic and/or pharmaceutical treatments in the oral region, especially treatments of the teeth or gums. 